scholarly journals The Controversies Surrounding Tocilizumab Administration Following Pathogen-Associated Molecular Pattern (PAMP) Induced by COVID-19

2020 ◽  
Author(s):  
Shayesteh Gheibi ◽  
Farhad Najmeddin ◽  
Bita Shahrami ◽  
Kourosh Sadeghi ◽  
Mojtaba Mojtahedzadeh
Keyword(s):  
Viral Infections ◽  
Virus Disease ◽  
Organ Damage ◽  
Immune Dysregulation ◽  
Global Pandemic ◽  
Molecular Pattern ◽  
Life Threatening ◽  
Molecular Patterns ◽  
Valuable Role

A new corona virus disease (COVID-19) has affected more than 17 million people worldwide so far, and has become a global pandemic. Since there is no definitive cure for this life threatening disease, many clinical studies are in progress in this regard. Pathogen-associated molecular patterns (PAMP) prompting by coronavirus seems to generate cellular, structural, and functional derangements induced by immune dysregulation as well as many biological abnormalities including cytokine storm. The role of IL-6 in viral pneumonia and also its inhibition impact on the prevention of organ damage are still unknown.IL-6 seems to behave as a double blade evil cytokine, by playing a valuable role in cell to cell natural physiological communication. Tocilizumab, as an inhibitor of interleukin (IL)-6, may interrupt the paracrine system while causing dissemination of bacterial, fungal, and other viral infections, especially COVID-19, who are at a high-risk for development of sepsis and life-threatening superinfection.

Treatment of ebola and other infectious diseases: melatonin “goes viral”

2020 ◽  
Vol 3 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Russel J Reiter ◽  
Qiang Ma ◽  
Ramaswamy Sharma
Keyword(s):  
Mortality Rate ◽  
Infectious Diseases ◽  
Hemorrhagic Shock ◽  
Safety Profile ◽  
Ebola Virus ◽  
Viral Infections ◽  
Virus Disease ◽  
Attractive Potential ◽  
Potential Treatment

This review summarizes published reports on the utility of melatonin as a treatment for virus-mediated diseases. Of special note are the data related to the role of melatonin in influencing Ebola virus disease. This infection and deadly condition has no effective treatment and the published works documenting the ability of melatonin to attenuate the severity of viral infections generally and Ebola infection specifically are considered. The capacity of melatonin to prevent one of the major complications of an Ebola infection, i.e., the hemorrhagic shock syndrome, which often contributes to the high mortality rate, is noteworthy. Considering the high safety profile of melatonin, the fact that it is easily produced, inexpensive and can be self-administered makes it an attractive potential treatment for Ebola virus pathology.  

scholarly journals Role of high dose IV vitamin C and zinc in coronavirus

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Arooj Fatima ◽  
Muhammad Usman Ali Khan ◽  
Mehkaar Najeeb ◽  
Muhammad Yasoob Ali Khan ◽  
Faiz Ul Haq
Keyword(s):  
Vitamin C ◽  
Viral Infections ◽  
Physiological Activity ◽  
Symptomatic Treatment ◽  
Primary Treatment ◽  
High Dose ◽  
Global Pandemic ◽  
The Common ◽  
Taste And Smell

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome- related coronavirus 2 (SARS-CoV- 2), is now considered as an ongoing global pandemic. Common symptoms include pyrexia, cough, dyspnea, fatigue, sore throat, and loss of sense of taste and smell. Complications that can result from more severe insult on lung tissue is pneumonia and acute respiratory distress syndrome (ARDS), which can further lead to septic shock. It is also not uncommon to find neurological symptoms in patients suffering from COVID-19. The primary treatment for COVID-19 is symptomatic treatment and supportive care. As there is no known vaccination and antiviral therapy for this disease, there is a desperate need to find an alternative to control and stop the spread of disease. Maintaining adequate micronutrient balance might enhance the immunity and protect from viral infections as well. Vitamin C and zinc helps in improving symptoms and shortening the duration of the common cold. Vitamin C (L-ascorbic acid) possesses pleiotropic physiological activity. High dose Vitamin C has shown to be effective against the common flu, rhinovirus, avian virus, chikungunya, Zika, ARDS, and influenza, and there is evidence that supports the protective effect of high dose IV vitamin C during sepsis-induced ARDS due to COVID-19. Zinc has a profound impact on the replication of viruses. Increasing intracellular zinc concentration along with pyrithione (zinc ionophore) has been shown to impair the replication of several RNA viruses efficiently, including poliovirus, influenza virus and several picornaviruses. A combination of zinc and can also inhibit the replication of SARS-coronavirus in cell culture.

scholarly journals Neutrophil Extracellular Traps (NETs) in Severe SARS-CoV-2 Lung Disease

2021 ◽  
Vol 22 (16) ◽  
pp. 8854
Author(s):  
Monika Szturmowicz ◽  
Urszula Demkow
Keyword(s):  
Lung Injury ◽  
Nuclear Dna ◽  
Viral Infections ◽  
Prognostic Significance ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Therapeutic Interventions ◽  
Extracellular Traps ◽  
Alveolar Capillary

Neutrophil extracellular traps (NETs), built from mitochondrial or nuclear DNA, proteinases, and histones, entrap and eliminate pathogens in the course of bacterial or viral infections. Neutrophils’ activation and the formation of NETs have been described as major risk factors for acute lung injury, multi-organ damage, and mortality in COVID-19 disease. NETs-related lung injury involves both epithelial and endothelial cells, as well as the alveolar-capillary barrier. The markers for NETs formation, such as circulating DNA, neutrophil elastase (NE) activity, or myeloperoxidase-DNA complexes, were found in lung specimens of COVID-19 victims, as well as in sera and tracheal aspirates obtained from COVID-19 patients. DNA threads form large conglomerates causing local obstruction of the small bronchi and together with NE are responsible for overproduction of mucin by epithelial cells. Various components of NETs are involved in the pathogenesis of cytokine storm in SARS-CoV-2 pulmonary disease. NETs are responsible for the interplay between inflammation and thrombosis in the affected lungs. The immunothrombosis, stimulated by NETs, has a poor prognostic significance. Better understanding of the role of NETs in the course of COVID-19 can help to develop novel approaches to the therapeutic interventions in this condition.

scholarly journals Aspergillus fumigatus LaeA-Mediated Phagocytosis Is Associated with a Decreased Hydrophobin Layer

2009 ◽  
Vol 78 (2) ◽  
pp. 823-829 ◽  
Author(s):  
Taylor R. T. Dagenais ◽  
Steve S. Giles ◽  
Vishukumar Aimanianda ◽  
Jean-Paul Latgé ◽  
Christina M. Hull ◽  
...  
Keyword(s):  
Cell Wall ◽  
Aspergillus Fumigatus ◽  
Wild Type ◽  
Macrophage Receptors ◽  
Macrophage Phagocytosis ◽  
Life Threatening ◽  
Carbohydrate Ligands ◽  
Cell Wall Carbohydrates ◽  
Molecular Patterns

ABSTRACT Aspergillus fumigatus is the causal agent of the life-threatening disease invasive aspergillosis. A. fumigatus laeA deletants, aberrant in toxin biosynthesis and spore development, are decreased in virulence. Among other characteristics, the decreased virulence is associated with increased spore susceptibility to macrophage phagocytosis. Three characteristics, cell wall microbe-associated molecular patterns (MAMPs), secreted metabolites, and rodlet content, thought to be important in macrophage-Aspergillus spore interactions were examined. Flow cytometry analysis of wild-type and ΔlaeA spores did not reveal any differences in surface-accessible MAMPs, including β-(1,3)-glucan, α-mannose, chitin, and other carbohydrate ligands. Blocking experiments with laminarin and mannan supported the conclusion that differences in cell wall carbohydrates were not responsible for enhanced ΔlaeA spore phagocytosis. Aspergillus spores have been reported to secrete metabolites affecting phagocytosis. Neither spent culture exchange, transwell, nor coincubation internalization experiments supported a role for secreted metabolites in the differential uptake of wild-type and ΔlaeA spores. However, sonication assays implicated a role for surface rodlet protein/hydrophobin (RodAp) in differential spore phagocytosis. A possible role of RodAp in enhanced ΔlaeA spore uptake was further assessed by RodAp extraction and quantification, where wild-type spores were found to contain 60% more RodAp than ΔlaeA spores. After removal of the surface rodlet layer, wild-type spores were phagocytosed at similar rates as ΔlaeA spores. We conclude that increased uptake of ΔlaeA resting spores is not associated with changes in secreted metabolite production of this mutant or surface carbohydrate availability but, rather, due to a decrease in the surface RodAp content of ΔlaeA spores. We theorize that RodAp acts as an antiphagocytic molecule, possibly via physicochemical means and/or by impeding MAMP recognition by macrophage receptors.

scholarly journals Emerging Role of the Inflammasome and Pyroptosis in Hypertension

2021 ◽  
Vol 22 (3) ◽  
pp. 1064
Author(s):  
Carmen De Miguel ◽  
Pablo Pelegrín ◽  
Alberto Baroja-Mazo ◽  
Santiago Cuevas
Keyword(s):  
Blood Pressure ◽  
Animal Models ◽  
Nlrp3 Inflammasome ◽  
Organ Damage ◽  
Subsequent Formation ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Inflammasomes are components of the innate immune response that have recently emerged as crucial controllers of tissue homeostasis. In particular, the nucleotide-binding domain, leucine-rich-containing (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex platform involved in the activation of caspase-1 and the maturation of interleukin (IL)-1β and IL-18, which are mainly released via pyroptosis. Pyroptosis is a caspase-1-dependent type of cell death that is mediated by the cleavage of gasdermin D and the subsequent formation of structurally stable pores in the cell membrane. Through these pores formed by gasdermin proteins cytosolic contents are released into the extracellular space and act as damage-associated molecular patterns, which are pro-inflammatory signals. Inflammation is a main contributor to the development of hypertension and it also is known to stimulate fibrosis and end-organ damage. Patients with essential hypertension and animal models of hypertension exhibit elevated levels of circulating IL-1β. Downregulation of the expression of key components of the NLRP3 inflammasome delays the development of hypertension and pharmacological inhibition of this inflammasome leads to reduced blood pressure in animal models and humans. Although the relationship between pyroptosis and hypertension is not well established yet, pyroptosis has been associated with renal and cardiovascular diseases, instances where high blood pressure is a critical risk factor. In this review, we summarize the recent literature addressing the role of pyroptosis and the inflammasome in the development of hypertension and discuss the potential use of approaches targeting this pathway as future anti-hypertensive strategies.

scholarly journals Vital Role of Technology on Fighting Covid-19 Pandemic

2021 ◽  
pp. 114-117
Author(s):  
Dr. Jayendrasinh Jadav ◽  
Krishna Kulin Trivedi
Keyword(s):  
21St Century ◽  
World Wide ◽  
Virus Disease ◽  
Vital Role ◽  
World Health ◽  
Global Pandemic ◽  
Global Trend ◽  
The World ◽  
Health Organization

The whole fights against the corona virus disease which is an infectious respiratory disease which has high transmissibility and has no medical therapy or vaccine which has been declared as the pandemic by the world health organization popularly known in short as WHO and is a global pandemic. The 21st century is the digital age and digitalization is the global trend. Technology has played a vital role in fighting with the COVID-19 Pandemic. The sudden world-wide pandemic forced to imposed lockdown during which there is digital surge. This research paper focuses on the vital role of technology in fighting the COVID-19 Pandemic.

scholarly journals ADP-heptose is a pathogen-associated molecular pattern of Shigella flexneri infection

2018 ◽  
Author(s):  
Diego García-Weber ◽  
Anne-Sophie Dangeard ◽  
Johan Cornil ◽  
Linda Thai ◽  
Héloise Rytter ◽  
...  
Keyword(s):  
Shigella Flexneri ◽  
Deletion Mutants ◽  
Gram Negative Bacteria ◽  
Biosynthesis Pathway ◽  
Inflammatory Gene Expression ◽  
Molecular Pattern ◽  
Pathogen Recognition Receptors ◽  
Molecular Patterns ◽  
Rule Out

ABSTRACTDuring an infection, the detection of pathogens is mediated through interactions between pathogen-associated molecular patterns (PAMPs) and pathogen recognition receptors. β-Heptose 1,7-bisphosphate (βHBP), a metabolite of the lipopolysaccharide (LPS) biosynthesis pathway, was recently identified as a PAMP of gram-negative bacteria. It was reported that βHBP sensing leads within minutes to oligomerization of the protein TIFA, a mechanism controlling NF-κB activation and pro-inflammatory gene expression. Here, we compared the ability of chemically synthesized βHBP and Shigella flexneri lysate to induce TIFA oligomerization in epithelial cells. In contrast to lysate, we found that βHBP fails to trigger rapid oligomerization of TIFA. βHBP only induces delayed signaling, suggesting that it has to be processed intracellularly to induce inflammation. By dissecting the LPS biosynthesis pathway with deletion mutants and functional complementation experiments, we show that ADP-D-glycero-β-D-manno-heptose and ADP-L-glycero-β-D-manno-heptose are the bacterial metabolites responsible for rapid TIFA oligomerization, and that they strongly induce interleukin-8 expression during S. flexneri infection. Altogether, our results rule out a major role of βHBP in S. flexneri infection and identify ADP-heptose as a new PAMP.

scholarly journals Myths and Facts: Chloroquine May Be A Potential Supportive/Therapeutic Drug in COVID-19 Treatment

2020 ◽  
Author(s):  
Muhammad Kashif ◽  
Muhammad Aamir ◽  
Sadia Minhas ◽  
Romeeza Tahir ◽  
Shah Jahan ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Viral Infections ◽  
Virus Disease ◽  
Antiviral Drug ◽  
Malaria Prevention ◽  
Therapeutic Drug ◽  
Therapeutic Role ◽  
Corona Virus ◽  
Simplex Virus

Quinine and its less toxic derivatives have served humanity for decades as potent antimalarial drugs. Emergence of drug resistance has narrowed the usage of these drugs in malaria prevention and treatment. Fortunately, these drugs have roles in the treatment of other diseases as well including rheumatic disorders and viral infections. Quinine derivatives have proven antiviral effects, especially against human immunodeficiency virus (HIV), Zika virus (ZiKV), herpes simplex virus (HSV), Ebola virus and dengue virus (DENV). The prophylactic and therapeutic role of Chloroquine/hydroxychroquine has become a topic of interest after the recent outbreak of novel Corona virus-19 (nCoV-19). This virus is also named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and WHO has officially named this disease as Corona virus disease 2019 (COVID-19). This lethal virus has affected almost 186 countries of the world till to date just in a period of four months of its outbreak. No approved antiviral drug is existed for the treatment of COVID-19. Therefore, this review is focused on potential prophylactic and therapeutic role of chloroquine/hydroxychlroquine for COVID-19.

scholarly journals Role of Biomarkers in the Diagnosis, Risk Assessment, and Management of Pulmonary Hypertension

2016 ◽  
Vol 11 ◽  
pp. BMI.S38323 ◽  
Author(s):  
Vanessa Rameh ◽  
Antoine Kossaify
Keyword(s):  
Risk Assessment ◽  
Pulmonary Hypertension ◽  
Organ Damage ◽  
Right Heart ◽  
Severe Condition ◽  
Pulmonary Arterial ◽  
Risk Assessment And Management ◽  
Valuable Role ◽  
Different Levels

Pulmonary hypertension is a severe and debilitating disease with no definite cure, and the domain of targeted therapies is a promising field for better management of this severe condition. The disease comprises pulmonary arterial remodeling, hypoxia, endothelial dysfunction, and inflammation, with subsequent organ damage including right heart and liver dysfunction. Biomarkers have a valuable role at different levels of the disease, from diagnosis to risk assessment and management, in order to decrease the burden of the disease in terms of both morbidity and mortality.

scholarly journals Role of Lopinavir/Ritonavir in the Treatment of Covid-19: A Review of Current Evidence, Guideline Recommendations, and Perspectives

2020 ◽  
Vol 9 (7) ◽  
pp. 2050 ◽  
Author(s):  
Simone Meini ◽  
Alberto Pagotto ◽  
Benedetta Longo ◽  
Igor Vendramin ◽  
Davide Pecori ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Respiratory Illness ◽  
Organ Damage ◽  
Current Evidence ◽  
Laboratory Studies ◽  
Scientific Societies ◽  
Pathogenetic Role ◽  
Proven Efficacy ◽  
Life Threatening

A life-threatening respiratory illness (COVID-19) due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus was first described in December 2019 in Wuhan (China), rapidly evolving into a pandemic. In the first phase, when the viral replication plays a pivotal pathogenetic role, antiviral drugs could be crucial in limiting viral-induced organ damage. Unfortunately, there are no specific antivirals of proven efficacy for COVID-19, and several drugs have been repurposed to face this dramatic pandemic. In this paper we review the studies evaluating lopinavir/ritonavir association (LPV/r) use in COVID-19, and previously in SARS and Middle East respiratory syndrome (MERS). We searched PubMed to identify all relevant clinical and laboratory studies published up to 15 May 2020; the guidelines on the use of LPV/r in COVID-19 were further directly searched on the website of the main international scientific societies and agencies. Available evidence is currently scarce and of low quality. The recommendations issued for COVID-19 vary from positions clearly against the use of LPV/r to other positions that are more favorable. In our opinion, despite the controversial results of an important randomized clinical trial, and some recommendations, clinicians should not abandon the use of LPV/r for the treatment of COVID-19, possibly using this drug inside a prospective randomized trial, waiting for the results of the numerous ongoing trials evaluating its efficacy.

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